DESCRIPTION: We have identified a total of seven genes or quantitative trait loci (QTLs) that determine loss of righting reflex (LORR) induced by ethanol. These loci have been named Lore I through 7 (Loss Of Righting: Ethanol). Together these genes explain more than 50% of the difference in ethanol-induced LORR between the LS and SS selected lines of mice. These QTLs are now identified only as relatively large genetic regions that are partially responsible for LORR differences. In our renewal we propose to pursue the next logical step: identification of the genes responsible for ethanol-induced LORR by molecular cloning of these genes. The major hurdles to be overcome in achieving this goal are: (1) localization of each Lore gene to as small a genetic region as possible: (Specific Aims A and B); (2) identifying and testing candidate genes within this area (Specific Aim C); (3) confirmation testing of proven candidate genes for involvement in the specification of LORR (future grants). After completion of Specific Aim A we will have defined a genetic region that could be as small as several cM; this will be narrowed down to a cM or less and moved to the molecular level (on the order of a few Mb of DNA)in Specific Aim B. Specific Aim C will identify and test candidate genes for subsequent transgenic tests.